Prostate cancer (PC) is the most common malignancy in males and the second leading cause of cancer-related deaths in the United States and Europe (Gronberg H. Lancet 2003 Mar. 8, 361(9360): 859-64). Detection of PC at an early stage by serum test for prostate specific antigen (PSA), and subsequent surgery and radiation therapy can cure the localized disease, but nearly 30% of treated PC patients suffer relapse (Han M, Partin A W, et al. J Urol 2001, 166: 416-9; Roberts S G, et al. Mayo Clin Proc 2001, 76: 576-81; Roberts W W, et al. Urology 2001, 57: 1033-7).
Despite high response rates and clinical benefits, androgen ablation therapy does not cure advanced or relapsed prostate cancer, because hormone refractory prostate cancer (HRPC) cells inevitably emerge and lead to cancer death. There are no effective treatments available for such HRPCs at present, and identification of novel molecular targets and therapeutic approach targeting them are urgently required. These HRPC cells not only grow hormone-independently, but also behave more aggressively as cancer cells and lead patients to death, which implicate that a number of other growth-promoting or malignant signaling pathways, bypassing the androgen receptor (AR) pathway, are activated in HRPC as well as AR signaling (Grossmann M E, et al. JNCI 2001, 93: 1687-97; Craft N, et al. Nature Med 1999, 5: 280-5; Bernard D, et al. JCI 2003, 112: 1724-31).